INHIBITION OF VASCULAR ENDOTHELIAL-CELL GROWTH-FACTOR ACTIVITY BY AN ENDOGENOUSLY ENCODED SOLUBLE RECEPTOR

Vascular endothelial cell growth factor, a mitogen selective for vascu lar endothelial cells in vitro that promotes angiogenesis in vivo, fun ctions through distinct membrane-spanning tyrosine kinase receptors. T he cDNA encoding a soluble truncated form of one such receptor, fms-li ke tyrosine kinase receptor, has been cloned from a human vascular end othelial cell library. The mRNA coding region distinctive to this cDNA has been confirmed to be present in vascular endothelial cells. Solub le fms-like tyrosine kinase receptor mRNA, generated by alternative sp licing of the same pre-mRNA used to produce the full-length membrane-s panning receptor, encodes the six N-terminal immunoglobulin-like extra cellular ligand-binding domains but does not encode the last such doma in, transmembrane-spanning region, and intracellular tyrosine kinase d omains. The recombinant soluble human receptor binds vascular endothel ial cell growth factor with high affinity and inhibits its mitogenic a ctivity for vascular endothelial cells; thus this soluble receptor cou ld act as an efficient specific antagonist of vascular endothelial cel l growth factor in vivo.